Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies

Chris R. Cardwell; Lars C. Stene; Johnny Ludvigsson; Joachim Rosenbauer; Ondrej Cinek; Jannet Svensson; Francisco Perez-Bravo; Anjum Memon; Suely G. Gimeno; Emma J.K. Wadsworth; Elsa S. Strotmeyer; Michael J. Goldacre; Katja Radon; Lee-Ming Chuang; Roger C. Parslow; Amanda Chetwynd; Kyriaki Karavanaki; Girts Brigis; Paolo Pozzilli; Brone UrbonaitĖ; Edith Schober; Gabriele Devoti; Sandra Sipetic; Geir Joner; Constantin Ionescu-Tirgoviste; Carine E. de Beaufort; Kirsten Harrild; Victoria Benson; Erkki Savilahti; Anne-Louise Ponsonby; Mona Salem; Samira Rabiei; Chris C. Patterson

doi:10.2337/dc12-0438

Breast-Feeding and Childhood-Onset Type 1 Diabetes

A pooled analysis of individual participant data from 43 observational studies

Chris R. Cardwell, PHD¹ ⇓,
Lars C. Stene, PHD²,³,
Johnny Ludvigsson, MD, PHD⁴,
Joachim Rosenbauer, MD, DIPL MATH⁵,
Ondrej Cinek, MD, PHD⁶,
Jannet Svensson, PHD⁷,
Francisco Perez-Bravo, PHD⁸,
Anjum Memon, MBBS, DPHIL⁹,
Suely G. Gimeno, DPH¹⁰,
Emma J.K. Wadsworth, PHD¹¹,
Elsa S. Strotmeyer, PHD¹²,
Michael J. Goldacre, FFPHM¹³,
Katja Radon, PHD¹⁴,
Lee-Ming Chuang, MD, PHD¹⁵,
Roger C. Parslow, PHD¹⁶,
Amanda Chetwynd, PHD¹⁷,
Kyriaki Karavanaki, MD, PHD¹⁸,
Girts Brigis, MD, PHD¹⁹,
Paolo Pozzilli, MBBS, MD²⁰,
Brone UrbonaitĖ, MD, PHD²¹,
Edith Schober, MD²²,
Gabriele Devoti, MD²³,
Sandra Sipetic, MD, PHD²⁴,
Geir Joner, MD, PHD²⁵,²⁶,
Constantin Ionescu-Tirgoviste, MD, PHD²⁷,
Carine E. de Beaufort, MD, PHD²⁸,
Kirsten Harrild, MSC²⁹,
Victoria Benson, PHD³⁰,
Erkki Savilahti, MD, PHD³¹,
Anne-Louise Ponsonby, MBBS, PHD³²,
Mona Salem, MD³³,
Samira Rabiei, MSC³⁴ and
Chris C. Patterson, PHD¹

¹School of Medicine and Dentistry, Queen’s University Belfast, Belfast, U.K.
²Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
³Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway
⁴Department of Clinical Experimental Medicine, Division of Pediatrics, Linkoping University Hospital, Linkoping, Sweden
⁵Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Institute at Duesseldorf University, Duesseldorf, Germany
⁶Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Motol, Czech Republic
⁷Pediatric Department, Herlev University Hospital, Herlev, Denmark
⁸Department of Nutrition, Faculty of Medicine, Laboratory of Nutritional Genomics, University of Chile, Santiago, Chile
⁹Division of Primary Care and Public Health, Brighton and Sussex Medical School and NHS Brighton and Hove, Brighton, U.K.
¹⁰Preventive Medicine Department, Federal University of São Paulo, São Paulo, Brazil
¹¹Cardiff Work Environment Research Centre, Cardiff University, Cardiff, U.K.
¹²Department of Epidemiology, Graduate School of Public Health, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, Pennsylvania
¹³Department of Public Health, Oxford University, Oxford, U.K.
¹⁴Institute and Outpatient Clinic for Occupational and Environmental Medicine, Hospital of the Ludwig Maximilian University Munich, Munich, Germany
¹⁵Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
¹⁶Paediatric Epidemiology Group, University of Leeds, Leeds, U.K.
¹⁷Mathematics and Statistics Department, Lancaster University, Lancaster, U.K.
¹⁸Second University Department of Pediatrics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
¹⁹Department of Public Health and Epidemiology, Riga Stradins University, Riga, Latvia
²⁰University Campus Bio-Medico, Rome, Italy
²¹Institute of Endocrinology of Lithuanian University of Health Science, Kaunas, Lithuania
²²Department of Paediatrics, Medical University of Vienna, Vienna, Austria
²³Department of Social Sciences and Communication, University of Salento, Lecce, Italy
²⁴School of Medicine, Institute of Epidemiology, Belgrade University, Belgrade, Serbia
²⁵Faculty of Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway
²⁶Department of Paediatrics, Oslo University Hospital, Oslo, Norway
²⁷Nutrition and Metabolic Diseases Clinic, N. Paulescu Institute of Diabetes, Bucharest, Romania
²⁸Clinique Pédiatrique Luxembourg, Luxembourg City, Luxembourg
²⁹Medical Statistics Team, University of Aberdeen, Aberdeen, U.K.
³⁰Cancer Epidemiology Unit, University of Oxford, Oxford, U.K.
³¹Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
³²Murdoch Children’s Research Institute, The Royal Children’s Hospital, Melbourne, Australia
³³Paediatrics Department, Ain Shams University, Cairo, Egypt
³⁴Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran

Corresponding author: Chris R. Cardwell, c.cardwell{at}qub.ac.uk.

Abstract

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.

RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.

RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I² = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I² = 0%). Adjustments for potential confounders altered these estimates very little.

CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Footnotes

This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0438/-/DC1.

Received March 5, 2012.
Accepted May 9, 2012.

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